Homodimerization of the human interleukin 4 receptor alpha chain induces C epsilon germline transcripts in B cells in the absence of the interleukin 2 receptor gamma chain

The cytokines interleukin (IL)-4 and IL-13 play a critical role in inducing CE germline transcripts and IgE isotype switching in human B cells, The IL-4 receptor (IL-4R) in B cells is composed of two chains, the IL-4-binding IL-4R alpha chain, which is shared with the IL-13R, and the IL-2R gamma (gamma c) chain, which is shared with IL-7R, IL-9R, and IL-15R, IL-4 induces Ce germline transcripts and IgE isotype switching in B cells from patients with gamma c chain deficiency, Induction of CE germline transcripts by IL-4 in B cells that lack the gamma c chain may involve signaling via the IL-13R, Alternatively, the IL-4R alpha chain may transduce intracellular signals that lead to CE gene transcription independently of its association with other chains, We show that ligand-induced homodimerization of chimeric surface receptors consisting of the extracellular and transmembrane domains of the erythropoietin receptor and of the intracellular domain of IL-4R alpha induces Janus kinase 1 (Jak1) activation, STAT6 activation, and CE germline transcripts in human B cell line BJAB, Disruption of the Jak1-binding proline-rich Box1 region of IL-4R alpha abolished signaling by this chimeric receptor, Furthermore, B cells transfected with a chimeric CD8 alpha/IL-4R alpha receptor, which is expressed on the cell surface as a homodimer, constitutively expressed CE germline transcripts, These results suggest that homodimerization of the IL-4R alpha chain is sufficient to transduce Jak1-dependent intracellular signals that lead to IgE isotype switching.